Amrinone suppresses the synthesis of tumor necrosis factor-alpha in human mononuclear cells

Tumor necrosis factor-alpha (TNF) exerts a wide spectrum of biological activities and contributes to the pathophysiology of septic shock. Elevated circulating levels of TNF have also been reported in patients with severe chronic heart failure. We studied the effect of amrinone, a class III cyclic nu...

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Bibliographic Details
Published in:Shock (Augusta, Ga.) Ga.), 1994-05, Vol.1 (5), p.377-380
Main Authors: Endres, S, Sinha, B, Fülle, H J
Format: Article
Language:English
Subjects:
Amrinone - pharmacology
Cell Line
Cyclic AMP - agonists
Cyclic AMP - metabolism
Humans
Lipopolysaccharides - pharmacology
Monocytes - drug effects
Monocytes - metabolism
Radioimmunoassay
Tumor Necrosis Factor-alpha - biosynthesis
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Summary:Tumor necrosis factor-alpha (TNF) exerts a wide spectrum of biological activities and contributes to the pathophysiology of septic shock. Elevated circulating levels of TNF have also been reported in patients with severe chronic heart failure. We studied the effect of amrinone, a class III cyclic nucleotide phosphodiesterase inhibitor used in the treatment of acute heart failure, on the synthesis of TNF in vitro. Peripheral blood mononuclear cells from healthy volunteers or cells of a permanent monoblast cell line were stimulated for 20 h with bacterial lipopolysaccharide and different doses of amrinone. TNF production is suppressed in a dose-dependent manner to a minimum of 9% of controls with 1000 microM of amrinone, reaching half-maximal inhibition at 80 microM amrinone. This effect appears to be mediated via cAMP, which accumulated nearly twofold in the presence of amrinone. Suppression of TNF synthesis by therapeutically administered phosphodiesterase inhibitors such as amrinone may contribute to their beneficial effect in the treatment of heart failure.
ISSN:1073-2322
DOI:10.1097/00024382-199405000-00011